I. Field of the Invention
The present invention relates generally to the field, including pulmonary arterial and pulmonary vascular hypertension, of medical diagnosis and specifically to a process of identifying patients with Pulmonary Hypertension (PH), including pulmonary arterial and pulmonary vascular hypertension and classifying the functional status of these patients to assess the severity of the disease. The present method provides a more sensitive, physiologic, and easier to use method than currently available classification systems. In addition, the present invention provides feedback during long-term follow-up and treatment in patients with PH.
II. Related Art
The early symptoms of PH—such as Dyspnea, dizziness and fatigue—are often mild and are common to many other conditions. At rest there are often no symptoms and no apparent signs of illness. As a result, diagnosis can be delayed for months or even years meaning that PH is frequently not recognized until the disease is relatively advanced.1 PH is often diagnosed only once other conditions have been investigated and ruled out.
The non-specific nature of symptoms associated with PH means that the diagnosis cannot be made on symptoms alone. A series of investigations is required to make an initial diagnosis, to refine that diagnosis in terms of clinical class of pulmonary hypertension, and to evaluate the degree of functional and hemodynamic impairment. Current PH evaluation and classification (type, functional capacity, hemodynamics) methods include blood tests and immunology, HIV test, abdominal ultrasound scan, 6-minute walk test (6-MWT), peak VO2, right heart catheterization, and vaso-reactivity testing. It is with exercise that the sympathetic and neuro-hormonal systems trigger increased vasoconstriction of the pulmonary arteriolar vascular beds, thus causing an elevation in pulmonary vascular resistance and reduced blood flow through the pulmonary vascular circuit. The reduced blood flow is mismatched to the air flow in the bronchioles and alveoli.
It is often that the exercise state is not evaluated by any pulmonary function parameters that truly represent gas exchange in the lungs. Instead, walking distance and peak oxygen uptake are measured.
A well-known current classification system was formulated by the New York Heart Association (NYHA) and the World Health Organization (WHO). The NYHA system places patients in one of four categories based on how much they are limited during physical activity.
TABLE 1NYHA/WHO Classification of Functional Statusof Patients with Pulmonary Hypertension1ClassSymptomatic profileClass IPatients with pulmonary hypertension but withoutresulting limitation of physical activity. Ordinaryphysical activity does not cause Dyspnoea or fatigue,chest pain or near syncopeClass IIPatients with pulmonary hypertension resulting in slightlimitation of physical activity. They are comfortable atrest Ordinary physical activity causes undue dyspnoea orfatigue, chest pain or near syncopeClass IIIPatients with pulmonary hypertension resulting in markedlimitation of physical activity. They are comfortable at rest.Less than ordinary activity causes undue dyspnoea orfatigue, chest pain or near syncopeClass IVPatients with pulmonary hypertension with inability to carryout any physical activiry without symptoms. These patientsmanifest signs of right heart failure. Dyspnoea and/or fatiguemay even be present at rest. Discomfort is increased by anyphysical activity.
The major shortcoming of the NYHA/WHO system is that it relies on subjective observations by the patient and interpretation of those observations by the physician.
The 6-minute walk test, while simple and convenient, has many limitations including issues relating to reproducibility, sensitivity, and essentially a plateau in functional assessment when patients have less functional impairment.
The logistics of performing an exercise test to maximal exertion, including laboratory staffing, direct physician supervision and test duration, in addition to the increased level of patient discomfort, does not lend to conducting this procedure in a serial fashion over short time intervals (i.e. several weeks-months). In addition, it has been found that maximum exercise levels are not representative of lower level, activities of daily living.